Abstract

Phosphoribosylpyrophosphate (PRPP) synthetase catalyzes the synthesis of PRPP, a critical substrate common to the de novo and salvage pathways of purine nucleotide synthesis. The PRPP synthetase reaction involves the transfer of the terminal pyrophosphate group of ATP (as a MgATP complex) to the C-1 carbon of ribose-5-P and is dependent on inorganic phosphate (Pi) and Mg2+ which serve as enzyme activators as well as cofactors. Activity of PRPP synthetase is inhibited by a number of phosphorylated compounds including the reaction products (PRPP) and AMP), purine, pyrimidine, and pyridine nucleotides and 2,3-DPG.1 Human PRPP synthetase is composed of a single polypeptide subunit2 the structural gene for which maps to the long arm of the X-chromasome.3 Under appropriate conditions of enzyme and effector concentration in vitro PRPP synthetase subunits are capable of reversible self-association to aggregates containing 2,4,8,16 and 32 subunits, with only the largest two of these containing significant enzyme activity.4